ctDNA is evolving as an important biomarker for ICI treatment response assessment in advanced melanoma. However, the utility of ctDNA monitoring during concurrent ICI with RT remains incompletely explored. In this multicenter, retrospective study, patients with unresectable stage III/IV melanoma treated with ICI and palliative RT were identified. Patients had retrospectively collected, tumor-informed, exome-based, ctDNA monitoring within 3 months following RT. 50 patients treated with ICI and palliative RT were analyzed. Patients with ctDNA clearance had significantly longer OS (HR 2.10, 95% CI 1.16-3.80, p=0.014) compared to those with increasing or decreasing and detectable ctDNA following RT. One-year OS was 85.9% with ctDNA clearance, 30.6% with decreasing ctDNA, and 22.0% for increasing ctDNA. In a multivariable analysis, both decreasing and increasing ctDNA were associated with worse OS compared with ctDNA clearance (HR 5.08 [95% CI, 1.26–20.48, p=0.022] and HR 9.83 [95% CI, 2.69–35.94, p< 0.001], respectively). Among patients with advanced melanoma treated with ICI and palliative RT, ctDNA clearance is associated with significantly improved OS compared to patients with detectable ctDNA within 3 months following RT. Ongoing studies are needed to understand the role of ctDNA in this population.

9533 Background: ctDNA is becoming a useful biomarker for ICI treatment response assessment in advanced melanoma. RT is capable of producing an abscopal effect, potentially enhancing ICI efficacy. The utility of ctDNA monitoring with concurrent ICI and RT remains incompletely explored. Here, we describe the clinical characteristics and survival outcomes of patients with advanced stage melanoma treated with ICI and palliative RT based on ctDNA dynamics. Methods: In this multicenter, retrospective study, patients with unresectable stage III/IV melanoma treated with ICI and palliative RT were identified. Patients had prospectively collected, tumor-informed, exome-based, ctDNA monitoring (Natera). Within 3 months prior to RT, patients had a baseline ctDNA level. Patients were separated into 3 cohorts based on nadir ctDNA dynamics within 3 months after RT. Those with undetectable ctDNA were categorized as “ctDNA cleared.” Patients with a positive fold ctDNA change were “increasing ctDNA” and negative fold change were “decreasing ctDNA.” Hazard ratios for overall survival (OS) probability were determined via log-rank tests and multivariate analysis (MVA) used cox proportional hazard models. Results: 50 patients treated with ICI and palliative RT were analyzed. Median follow up was 8.0 months from RT start. Median age was 65 (24-86) and median baseline ctDNA level was 8.9 MTM/mL (0-11390 MTM/mL). Melanoma primaries included: 82% (41) cutaneous, 10% (5) mucosal, 8% (4) unknown primary. ICI regimens included 70% (35) ipilimumab/nivolumab, 16% (8) nivolumab/relatlimab, 2% (1) anti-PD-1/investigational ICI, 12% (n=6) anti-PD-1 monotherapy. 20 patients had ctDNA clearance, 12 patients had decreasing ctDNA, and 18 patients had increasing ctDNA following RT with ICI. The most common RT sites were the CNS (50%, n=25) and skin/soft tissue (24%, n=12), followed by lymph nodes and bone (each 14%, n=7), and lung and liver (each 6%, n=3). Patients with ctDNA clearance had longer OS (p=0.001) compared to those with increasing or decreasing and detectable ctDNA following RT. One year OS was 85.9% with ctDNA clearance, 30.6% with decreasing ctDNA, 22.0% for increasing ctDNA. In a MVA adjusting for age, M substage, radiation site, and melanoma subtype, both decreasing and increasing ctDNA were associated with worse OS compared with ctDNA clearance (HR 5.08 [95% CI, 1.26–20.48, p=0.022] and HR 9.83 [95% CI, 2.69–35.94, p<0.001], respectively). Conclusions: Among patients with advanced melanoma treated with ICI and palliative RT, ctDNA clearance is associated with significantly improved OS compared to patients with detectable ctDNA within 3 months following RT. Ongoing prospective studies are needed to understand the long-term clinical impact of RT on ICI-treated patients with melanoma, and better define the role of ctDNA monitoring for this population.

9534 Background: ctDNA predicts relapse in resected tumors, but its role in advanced disease is less defined. We previously reported that early ctDNA changes at 3-4 weeks after ICI initiation can inform treatment response and survival. In this study, we attempt to identify the optimal timing of ctDNA dynamics within 90 days at various windows to better associate with ORR, PFS, and OS outcomes in patients (pts) with advanced stage melanoma treated with ICI. Methods: We performed a multicenter retrospective analysis using a personalized tumor-informed ctDNA assay (Natera) on prospectively collected plasma from pts with unresectable stage III/IV melanoma treated with anti-PD-1-based therapy. ctDNA was assessed at baseline and within 90 days of ICI initiation, stratified by ≤30, 31-60, and 61-90 days. Logistic regression evaluated associations between ctDNA change (decrease/stable vs increase) and ORR. Cox proportional hazards models assessed PFS and OS. Pearson (ORR) and Spearman (PFS, OS) correlations were used for continuous ctDNA analyses. Results: Among 182 pts, 80% had cutaneous, 11% mucosal, and 9% unknown primary melanoma; 23% had unresectable stage III and 77% stage IV disease. Treatments included ipilimumab/nivolumab (55%), nivolumab/relatlimab (24%), and anti–PD-1 monotherapy (20%). Median follow-up was 12.1 months. Decreasing/stable ctDNA at all timepoints was strongly associated with ORR (p<0.0001), with the greatest effect at 31-60 days (OR 25.38, 95% CI 7.12-90.45). Similar patterns were observed for survival, with improved PFS across all windows and strongest separation at 61-90 days (HR 0.170, 0.101-0.288). OS was likewise improved, most notably at 61-90 days (HR 0.137, 0.058-0.321). Continuous ctDNA change correlated with ORR (r -0.51 to -0.63) and PFS (ρ -0.35 to -0.47); OS correlations were weaker but significant at 61-90 days (ρ -0.21). See Table 1. Conclusions: While ctDNA dynamics within 30 days showed prognostic value, associations with ORR, PFS, and OS were strongest and most consistent at 31–60 and 61–90 days. Prospective studies are needed to validate ctDNA for ICI treatment monitoring. Association of ctDNA dynamics with outcomes by time interval. ≤30 days 31-60 days 61-90 days ORR (OR, 95% CI) 15.28 (5.58–41.78), p<0.0001 25.38 (7.12–90.45), p<0.0001 17.82 (5.66–56.08), p<0.0001 PFS (HR, 95% CI) 0.373 (0.224-0.621), p<0.0001 0.233 (95% CI 0.139-0.388), p<0.0001 0.170 (0.101-0.288), p<0.0001 OS (HR, 95% CI) 0.477 (0.237-0.961), p=0.038 0.392 (95% CI 0.185-0.831), p<0.015 0.137 (0.058-0.321), p<0.0001 ORR (Pearson, r) -0.553, p<0.0001 -0.628, p<0.0001 -0.513, p<0.0001 PFS (Spearman, ρ) -0.352, p<0.0001 -0.438, p<0.0001 -0.473, p<0.0001 OS (Spearman, ρ) -0.128, p=0.168 -0.104, p=0.240 -0.210, p=0.0171

PURPOSE:To evaluate the differences in the incidence and severity of immune-related adverse effects (irAEs) between the pembrolizumab 21-day dosing schedule and the 42-day dosing schedule. METHODS:Patients with solid tumor malignances and no previous immunotherapy exposure were included. This case-control study compared patients on pembrolizumab 200 mg every 21 days with those on 400 mg every 42 days in a 2:1 ratio. The primary outcome was the rate of all grades of irAEs. RESULTS:A total of 160 patients who received treatment every 21 days and 80 patients who received treatment every 42 days were evaluated. All-grade irAEs occurred in 33.1% (53/160) and 32.5% (26/80) of patients in the 21-day group and the 42-day group, respectively. Regarding severe irAEs (grade 3 or worse), these occurred in 32.1% (17/53) and 23.1% (6/26) of patients in the 21-day and 42-day cohorts, respectively (P = 0.444). Additionally, no significant association was found between dosing schedule and steroid initiation (P = 0.595) or treatment discontinuation (P = 0.192). CONCLUSION:The comparison of the 21-day and 42-day pembrolizumab dosing cohorts revealed similar irAE rates and severity of toxicities. Rates of steroid initiation for irAE management and permanent treatment discontinuation due to irAE did not significantly differ between dosing schedules. While severe irAEs correlated with treatment discontinuation, dosing schedule did not differentially affect this outcome. Overall, extending the pembrolizumab dosing interval to 42 days appears safe while maintaining an irAE profile comparable to that with the standard 21-day schedule.

TPS12172 Background: Programmed cell death-1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, are widely used in treating solid tumors. These inhibitors have multiple FDA-approved dosing schedules. Extended-interval, higher-dose regimens offer patient convenience and health-system efficiencies. However, there is limited comparative prospective data evaluating immune-related adverse events (irAEs) across different dosing strategies. Our study aims to evaluate this important safety question in routine clinical practice. Methods: ImmuRAd is an investigator-initiated, open-label, randomized late phase trial. Adults (≥18 years) with histologically or cytologically confirmed solid tumor malignancies who are scheduled to receive standard-of-care PD-1 inhibitor-based therapy in any disease setting or line of therapy are eligible for the study. Participants are randomly assigned to one of two pre-defined standard dosing strategies based on their physician-selected PD-1 inhibitor cohort. In the nivolumab cohort, patients are randomized 1:1 to receive nivolumab 240 mg every 2 weeks or nivolumab 480 mg every 4 weeks. In the pembrolizumab cohort, patients are randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks or pembrolizumab 400 mg every 6 weeks. Route of administration is at the discretion of the investigator and can be given intravenous or subcutaneous. After completing 12 weeks of therapy, patients meeting predefined treatment-tolerance criteria may transition to extended-interval dosing at the discretion of the treating investigator. The primary objective is to determine the proportion of patients experiencing grade ≥3 immune-related adverse events (CTCAE v5.0) in each dosing arm within each cohort. Secondary endpoints include the incidence of all-grade immune-related adverse events, the time to resolution of these adverse events, treatment discontinuation due to immune-related adverse events, the overall response rate (for patients with measurable disease), progression-free or disease-free survival, and overall survival. Exploratory analyses will investigate the associations between immune-related adverse events and factors such as tumor type, treatment setting, microsatellite instability status, tumor mutational burden, and NGS biomarker profiles. The planned sample size is 192 evaluable patients (96 per cohort and 48 per arm). The study will enroll patients over a period of 24 months and will have a follow-up period of up to 2 years. In this IRB approved clinical trial, safety oversight will be provided by the institutional Data Safety Monitoring Committee. Trial Status: The study is actively enrolling at The University of Kansas Cancer Center and affiliated network sites. Clinical trial information: NCT07174453 .

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine form of skin cancer. This case report describes a 70-year-old Hispanic male with stage IIA MCC of the upper back which rapidly progressed during hospitalization for severe COVID-19 infection requiring ventilatory support. After resolution of his severe acute illness, he received one dose of anti-PD-1 therapy and single-fraction radiotherapy to his primary lesion for local control. His tumor then underwent a rapid regression and he completed 17 cycles of immunotherapy with a complete clinical and radiologic response sustained more than 4 years. This case illustrates a possible synergistic effect of radiation therapy and immune checkpoint inhibition after rebounding immune-system hyperactivation from infection with COVID-19.

11068 Background: A recent ASCO report highlighted improving patient access to cancer clinical trials as a fundamental priority. Although prior research found that 19% of participants in NCI-sponsored trials reside in rural areas, there is substantial heterogeneity in the classification of rurality. In addition, sociodemographic characteristics across different levels of rurality are unknown. In this analysis, we evaluated the prevalence and trends over time in trial enrollment by categories of rurality. Methods: We analyzed pooled data from phase II, II/III, and III trials conducted by the SWOG Cancer Research Network from 1992-2022. Rurality was defined by linking patient zip code to the Rural-Urban Continuum Codes, and categorized into four groups (large urban, small urban, rural, frontier). Baseline and patient demographic data were obtained from trial registration forms. Neighborhood deprivation, based on the Area Deprivation Index, was derived from patient zip code. The associations between rurality and patient characteristics were evaluated using multivariate logistic regression with covariate adjustments. Rurality enrollment was compared to corresponding overall US rurality estimates during the same period. Results: In total, N = 39,729 patients enrolled in 69 trials in brain, breast, GI, GU, gynecological, head and neck, lung, sarcoma, melanoma, and hematologic cancers were examined. Across the geographic groups, 52.2% lived in large urban, 30.9% lived in small urban, 11.6% lived in rural, and 5.4% lived in frontier areas, compared to corresponding US population estimates of 56.0% large urban, 28.6% small urban, 10.3% rural, and 5.0% frontier. Patients residing in frontier areas were nearly 80 times as likely to live in the highest versus lowest deprivation areas (OR = 78.37, 95% CI, 64.71-94.92, p < .0001). Similar though less pronounced associations were found among patients from rural and small urban areas (p < .0001). Frontier patients were more likely to be on Medicare (OR = 1.96, 95% CI, 1.66-2.30, p < .0001). Over the 30-year study period, trial enrollment among patients from frontier areas has decreased over time relative to the US population, whereas trial enrollment of patients from large urban areas has increased. Conclusions: Patients from rural and frontier areas are well-represented in SWOG clinical trials, however, enrollment among patients from frontier areas has shown a declining trend. Strong representation of patients with cancer from rural areas enhances the generalizability of trial findings. Given ongoing changes to healthcare, declining representation from frontier areas is likely to continue without targeted interventions. Further research is needed to expand access to care in these vulnerable areas and guide efforts that ensure adequate socioeconomic support for all patients, regardless of their geographic locale.

PURPOSE Multiple reports have suggested that receiving immunotherapy infusions earlier in the day is associated with improved outcomes, including longer overall survival (OS) and lower toxicity rates. However, the definition of early varies between publications. Reports also fail to account for confounding factors (including distance to infusion center), are subject to survivor bias (analyzing postbaseline factors at baseline), and do not adjust P values for multiple comparisons when evaluating multiple potential thresholds for early versus late time of day of infusion. METHODS We analyzed a previously reported multicenter clinical trial evaluating pembrolizumab as adjuvant therapy for participants with resectable high-risk melanoma. Standard statistical methodologies that account for potential biasses were used to evaluate the association between time of day of infusion and clinical outcomes. RESULTS A total of 628 participants received pembrolizumab and had time of first infusion recorded. The median age was 55 years, range, 20-82. Odds of infusion before 11:00 hours increased by 32% over 12 months of therapy ( P = .013). Participants living further from their treating institution had later infusion times on average: odds of infusion before 11:00 decreased by 9% for each additional 50 miles ( P = .017). The optimal cut point for first infusion time for OS was 15:48 with hazard ratio (HR) = 1.40; changing the cut point by 30 minutes earlier to 15:18 decreased HR to 0.98, indicating lack of robustness of the threshold. No significant association was identified between proportion of early infusions and outcomes in multivariable time-dependent Cox regression models. CONCLUSION In this multicenter trial of adjuvant pembrolizumab for participants with high-risk melanoma, analyses that account for common sources of bias found no significant association between recurrence-free or OS and time of day of infusion.

e21543 Background: Circulating tumor DNA (ctDNA) is an emerging biomarker of progression and relapse in multiple cancers. Our earlier single-center data demonstrated that site of melanoma relapse impacted the sensitivity of ctDNA detection. In this multi-institutional study, we further examined the prognostic implications between ctDNA detection and melanoma relapse site. Methods: A retrospective cohort analysis was performed across three centers using a personalized, tumor-informed ctDNA assay (Natera) on prospectively collected plasma from patients with melanoma from December 2021 to January 2025 with longitudinal follow up. Inclusion criteria were patients with no evidence of disease (NED) following definitive surgery or clinical remission with systemic therapy; and undetectable ctDNA. Sensitivity of ctDNA detection at biopsy- and/or radiographically confirmed relapse was evaluated, along with overall survival (OS) from date of relapse to date of death or last follow-up. Analyses were stratified based on anatomic sites of relapse. Logistic regression was used to evaluate predictors of ctDNA detection. Log-rank p-values and Cox proportional hazards were calculated for OS measurements. Results: Of 284 patients on longitudinal MRD surveillance, 78 (27.5%) had confirmed relapse. Of these, 75 (96.2%) had NED following surgery and 3 (3.8%) had clinical remission with systemic therapy, with 49 (62.8%) resected stage II/III, 26 (33.3%) resected stage IV, and 3 (3.8%) unresectable stage III/IV in remission. Primary sites included 61 (78.2%) cutaneous, 12 (15.4%) mucosal, and 5 (6.4%) unknown. ctDNA was detected at relapse in 40/78 patients (51.3% sensitivity). Similar to prior data, sensitivity varied by relapse site with 84.6% (22/26) for lymph node (LN) relapse and 28.6% (6/21) for skin/soft tissue (SST) relapse. LN metastases (OR = 10.4, 95% CI 3.1 – 34.8; p < 0.001) and multiple (2+) metastatic sites (OR = 4.43, 95% CI: 1.13 – 17.4; p = 0.037) were associated with detectable ctDNA at relapse, while SST metastases (OR 0.27 (95% CI: 0.09 – 0.80; p = 0.021) were associated with an undetectable ctDNA. Median follow-up time from relapse was 13.4 months. Survival analysis from time of relapse showed decreased OS in those with undetectable versus detectable ctDNA (log-rank p = 0.041; HR 0.321, 95% CI: 0.102 – 1.011), including in the SST relapse subgroup (log-rank p = 0.0016; HR not estimable). Conclusions: Detectable ctDNA at the time of melanoma relapse appears to be associated with inferior OS. ctDNA sensitivity varied by site of relapse, with improved survival observed for those with undetectable ctDNA at relapse. These findings support the prognostic relevance of ctDNA while highlighting important site-specific limitations, warranting validation in larger prospective cohorts.

Desmoplastic melanoma is a distinct subtype of melanoma known to have preexisting immune infiltrates and high ultraviolet light damage, resulting in a high tumor mutational burden. We hypothesized that this may result in high response rates with single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort clinical trial testing the activity of pembrolizumab in patients with surgically resectable (cohort A) and unresectable (cohort B) desmoplastic melanoma. Here we report on the cohort B single-arm clinical trial, which enrolled 27 patients with unresectable desmoplastic melanoma receiving pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years, with the primary endpoint of complete response rate. The complete response rate was 37% (95% confidence interval: 19-58%), and the post hoc endpoint of objective response rate was 89% (95% confidence interval: 71-98%). The estimated secondary endpoints of 3-year melanoma-specific progression-free survival and overall survival were 84% and 96%, respectively, with only one patient having died from melanoma progression. Ten patients (37%) experienced grade 3 or 4 adverse events, and nine patients (33%) discontinued treatment because of adverse events. Patients with advanced desmoplastic melanoma have a high response rate to single-agent PD-1 blockade therapy, supporting single-agent anti-PD-1 as the treatment of choice, but are limited by a frequency of toxicities that is numerically higher than in other patient populations. ClinicalTrials.gov identifier: NCT02775851.

CLINICAL TRIAL REGISTRATION:NCT06151847.

e23012 Background: Medications given to facilitate general anesthesia are known to impact recovery and may impact cancer outcomes after surgery. Most general anesthesia is facilitated with inhalational anesthesia (IA) while recent data suggests propofol-based total intravenous anesthesia (TIVA) results in improved patient recovery, lower rates of tumor recurrence, and improved overall survival in several solid tumors. We attempted to analyze the impact that anesthetic approach (TIVA vs IA) had on the outcome of several recent landmark RCTs where surgery requiring general anesthesia was central to the oncologic intervention. Methods: We proposed a secondary analysis of six RCTs whose primary outcome was published between 2019 and 2024 where surgery requiring general anesthesia was central to the oncologic intervention. Trial data was requested through correspondence with the authors or official data requests as appropriate. Results: Two of the six studies do not share data, prohibiting secondary analysis. In the other four trials, none captured anesthetic data. We then queried the case report forms for two ongoing international RCTs we are currently participating in. Of these, neither collect medications delivered during surgery. In total, of the eight RCTs queried (six published, two enrolling), we were unable to perform secondary analysis of the impact anesthetic approach has on cancer outcomes in all eight. Conclusions: We were not able to use secondary analysis of RCT data to investigate the impact that anesthetic approach (TIVA vs IA) has on cancer recurrence and overall survival. Currently, the choice between delivering TIVA and IA is made largely by anesthesiologist preference without prospectively collected data to validate the retrospective observation that TIVA results in lower recurrence and improved overall survival. Electronic medical records capture anesthetic data, but if it is not included within the case report forms on prospective RCTs, secondary analysis is impossible. Collection of anesthetic data during RCTs would allow the study of the impact anesthesia has on cancer outcomes and should be a common part of data collection on surgically focused cancer trials. NCT Pub Date Method of Request Data Availability NCT01216644 5/11/19 Data sharing statement Data not shared NCT02562716 1/21/21 Email with NCTN Data Archive Administrator Anesthesia data not captured NCT01804790 5/5/21 Email with corresponding author Anesthesia data not captured NCT02998528 4/11/22 Data sharing statement Data not shared NCT03698019 3/1/23 Email with NCTN Data Archive Administrator Anesthesia data not captured NCT04949113 6/2/24 Email with PI Anesthesia data not captured NCT03860883 Not yet published Query of case request form Anesthesia data not captured NCT04031677 Not yet published Query of case request form Anesthesia data not captured

Abstract Desmoplastic melanoma is a rare subtype of cutaneous melanoma defined by extensive fibrosis (desmoplasia), and at the same time has pre-existing immune infiltrates and a high tumor mutational burden (TMB) resulting from exposure to ultraviolet (UV) light, which we hypothesized may result in high response rates to single-agent anti-programmed death protein 1 (PD-1) therapy. SWOG S1512 was a two-cohort phase 2 clinical trial: i) Cohort A included 28 eligible patients with surgically resectable desmoplastic melanoma who received a median of 3 infusions (range 1- 4) of neoadjuvant pembrolizumab 200 mg every 3 weeks, followed by surgical excision. pCR rate was 57% (95% CI: 37%-76%, p<0.001); none of the patients received adjuvant pembrolizumab (Kendra et al. ASCO 2022). ii) Cohort B included 27 eligible patients with unresectable desmoplastic melanoma who received a median of 15 infusions (range 1- 34) of pembrolizumab, 200 mg IV every 3 weeks. The objective response rate was 89% (95%, CI:71%-98%; Kendra et al. AACR 2023). At 3 years of follow-up, 13 patients have died (4 cohort A, 9 cohort B). Causes of death were: melanoma (1), cardiac (4), infections (2), stroke (1), pulmonary fibrosis (1), kidney failure (1), acute myelogenous leukemia (1), brain bleed related to a fall (1), and unknown (1). The combined 3-year melanoma-specific survival is 96% (n=55, 95%CI 87%-99%). In conclusion, patients with desmoplastic melanoma are exceptional responders to single-agent PD-1 blockade therapy, leading to long-term responses. Funding for this research was provided by NIH/NCI grants: U10CA180888 and U10CA180819 (SWOG); and in part by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USAFigure 1. Melanoma-specific survival in the combined cohorts A and B of S1512 (n = 55) at 3-year follow up. Death from other causes were treated as competing risks using the Fine-Gray model. Citation Format: Kari L kendra, shay l Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M Campbell, William Carson III, David Wada, Jose A Plaza, Jeffery A Sosman, Gino In, Alexandra P Ikeguchi, John Hyngstrom, Andrew Brohl, Bartosz Chmielowski, Nikhil Khushalani, Joseph Markowitz, George Negrea, Samer Kasbari, Gary C Doolittle, Umang Swami, Toni Roberts, Marcus Monroe, Carlo Contreras, Edmidio Medina, Ignacio Baselga-Carretero, Cynthia R Gonzalez, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Min Chen, nataly Nasar Al-Deen, Kenneth F Grossman, Vernon Sondak, elad sharon, Sapna P Patel, james moon, Michael C Wu, Antoni Ribas. High melanoma-specific survival in patients with desmoplastic melanoma treated with single agent anti-PD-1 in SWOG S1512 [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr PR006.

Abstract Background: ASCO has reaffirmed critical role of early phase (EP) clinical trials (CT) in cancer research and treatment that patients (pts) may achieve improvement in quality of life, experience psychological and direct medical benefits. Disparities in access and participation to CT exist and are more profoundly seen in EP CT with challenge of engaging underrepresented populations (UP) in EP CT which are often complex and only available at larger cancer centers in metropolitan areas. NCI’s Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP.2020) helped bring EP CT to UP. To determine the impact of financial toxicity (FT) as a barrier specific to EP CT participation of UP, the validated COST-FACIT tool was used to survey cancer pts undergoing treatment at the University of Kansas Cancer Center. Methods: This study was approved by our Institutional Review Board (Study 00150640). During routine scheduled visits, pts completed COST-FACIT survey on touch screen tablet. A list of validated questions on EP CT awareness, access, and willingness to participate were included in the survey. Pts responded to 12-item COST-FACIT questionnaire describing the relationship between financial stress and treatments (scale 0 to 4). The score was computed using responses captured from COST-FACIT. Based on literature, scores <26 were determined to be higher FT. Two-sided Fisher's Exact Tests were used to test for a significant association at an alpha level of 0.05. UP included racial and ethnic minorities, low socioeconomic status, low education, and rural. Results: Of 108 pts, 101 completed surveys. 45% identified as female and 55% as male. 11.2% 18–35 years (yrs) of age, 13.9% 36 –50 yrs, 24% 51–65 yrs and 54% >65 yrs. 62.4% were white, 17.8% black, and 19.8% others (Asian or Native American). 8.9% completed <12th grade, 23.8% completed high school, 29.7% have some college experience, 22% completed college and 16% have master’s/doctoral degree. COST-FACIT mean score was 25.7 (SD 10.4, r^2 of 0.48) showing significant financial stress. 46% of pts had scores <26. Pts 18-35 yrs (p=0.02), 36–65 yrs (p=0.00), had yearly incomes of >150,000 (p=0.02) or unaware of their yearly income (p=0.05) were more likely to have significant FT. Pts with < 12th grade (14.89%) or some college experiences (34.09%) were likely to have significant FT. Pts identifying as Asian or Native American were more likely to experience FT than white or black. Conclusion: Almost half of our pts suffer from significant FT creating disparities in EP CT access and participation. Data suggest ages 35-65 yrs, low levels of education, and races other than white and black experience higher levels of FT that is a barrier to EP CT participation. These data support our ongoing efforts to bring innovative EP CT to everyone including the VA and our other outreach partners with higher concentrations of UP. Data on rural and health professional shortage areas will be reported during the meeting. This project was supported in part by The University of Kansas Cancer Center P30CA168524. Citation Format: Kamiyah Hicks, Anusha Chidharla, Dinesh Pal Mudaranthakam, Hope Krebil, Issa Espinoza, Asuka Suzuki, Sam Pepper, Angelica Allen, Jill Hamilton - Reeves, Debra Sullivan, Anna Arthur, Saqib Abbasi, Anup Kasi, Rahul Parikh, Elizabeth Wulff - Burchfield, Al - Ola Abdallah, Lori Barbosa, Erin Carroll, Jennifer Heins, Tara Lin, Gary Doolittle, Weijing Sun, Joaquina Baranda. The impact of financial toxicity as a barrier to access and participation in early phase clinical trials for underrepresented populations using the COST–FACIT tool [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B142.

Introduction Hematological neoplasms such as multiple myeloma and B-cell lymphomas benefit from targeted therapies such as chimeric antigen receptor therapy (CAR T). FDA-approved drugs such as tisagenlecleucel, axicabtagene ciloleucel, and others offer outpatient administration, improving post-therapy quality of life. CAR T-cell therapy demonstrates promise against solid tumors, but hurdles such as heterogeneous antigen presentation and barriers hamper efficacy. To address challenges in CAR T therapy for solid tumors, solutions such as localized delivery, chemokine receptor expression, anti-VEGF receptors, and engineered cytokines/FAP are proposed. Clinical trials targeting various antigens such as TnMUC1, mesothelin, and CD19 are ongoing, but none are approved yet. This review offers insights into CAR T's potential in solid tumor treatment. Methods Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a retrospective systematic review examined CAR T clinical trials targeting solid tumors from 2018 to 2023 on ClinicalTrials.gov. Trial variables including phase, status, sponsors, and endpoints were analyzed. Results This cross-sectional systematic review encompassed a review of 110 listed clinical trials, ultimately including 103 clinical trials with 4849 enrolled or expected patients. A trial was excluded if a CAR T construct was not a part of the trial methodology. The majority are phase I (73.8%), followed by phases I and II (18.4%), with 33 (32.1%) industry-sponsored and 70 (67.9%) non–industry-sponsored. Trial slots increased steadily from 2018 to 2023, peaking at 1594, with 84% conducted outside the United States (US). There was a significant increase in the number of new clinical trials, especially non-US sponsors, compared to US sponsors. Only 19 trials (18%) are/were being conducted in the United States in the studied time. Thirty-three unique molecular targets were explored, with mesothelin (17%) and claudin protein family (13%) being the most targeted. Primary outcomes focused on safety. Four trials were terminated due to adverse effects. Conclusion CAR T's success in hematologic malignancies has created great hope in solid tumor malignancies, although differences between the 2 categories temper this hope. A substantial effort is being made worldwide to improve these technologies, resulting in unique strategies for treating solid tumors. The United States lags in clinical trial efforts compared to other nations.

TPS9608 Background: Metastatic melanoma (MM) patients who have progressed following immune checkpoint inhibitors (ICI; anti–PD-1/CTLA-4 therapy) and targeted agents (BRAF/MEK inhibitors) have limited treatment options and dismal prognosis. An autologous tumor-infiltrating lymphocytes (TIL) therapy (LN-144, lifileucel) has demonstrated efficacy and durable responses in heavily pretreated advanced melanoma. In a phase II study of TIL therapy (lifileucel) with traditional lymphodepletion (LD), using fludarabine 25 mg/m2 for 5 days and cyclophosphamide (Cy) 60 mg/kg for 2 days, in 153 MM patients previously treated with ICI and BRAF/MEK inhibitors, an overall response rate (ORR) of 31% was noted, and the median duration of response (DOR) was not reached after 27.6 month follow up. We hypothesize that a reduced dose of Flu/Cy LD for TIL therapy will have similar TIL expansion and persistence post-infusion, resulting in similar efficacy with a reduced toxicity profile. Methods: Study NCT06151847 is a single-center, open-label phase II pilot trial evaluating the efficacy, in vivo persistence, and safety of TIL therapy after reduced dose Flu/Cy LD. Key inclusion criteria include unresectable or metastatic melanoma (stage IIIC-IV) with disease progression after one or more lines of therapy. Four of the 12 planned patients have been enrolled as of February 2, 2024. Central TIL manufacturing from at least a 1.5 cm tumor specimen involves ex vivo expansion through cell culture in the presence of the interleukin (IL)-2 and an anti-CD3 monoclonal antibody (1-150 x109 viable cells). Patients will receive an outpatient reduced-dose Flu/Cy LD regimen of Flu (30 mg/m2 on days -4, -3, -2, -1) and Cy (750 mg/m2 on days -4, -3, -2). Infusion of TIL will be performed on day 0 followed by high-dose IL-2 (600,000 IU/kg up to 6 doses). The primary objective will be to ascertain TIL persistence using T-cell receptor (TCR) sequencing at day 42 which will be compared to historical data already generated utilizing traditional Flu/Cy LD. The secondary objectives will be to evaluate the efficacy parameters including ORR, DOR, progression-free survival (PFS), and overall survival (OS), and the safety profile of TIL in combination with a reduced dose Flu/Cy LD regimen. Exploratory objectives will involvecorrelative analyses to characterize the immunome and microenvironment. If TIL persistence is roughly equivocal between the reduced and high-dose Flu/Cy LD regimens, the design of a larger-scale trial using reduced-dose Flu/Cy LD for TIL therapy may be considered. Study follow-up will continue for one year. Clinical trial information: NCT06151847 .

Background:Clinical trial participation can improve overall survival and mitigate healthcare disparities for gynecologic cancer patients in low-volume community centers. This study aimed to assess the effectiveness of a centrally regulated but administratively decentralized electronic screening log system to identify eligible patients across a large catchment area for a National Cancer Institute (NCI)-designated cancer center's open clinical trials. Methods:Electronic screening log data collected between 2014 and 2021 from ten community partner sites in a single NCI-designated cancer center's catchment area were reviewed retrospectively. Clinical factors assessed included cancer site, primary versus recurrent disease status, and histology. Identification efficiency (the ratio of patients screened identified with an available trial) was calculated. Identification inefficiencies (failures to identify patients with a potentially relevant trial) were assessed, and etiologies were characterized. Results:Across ten community partner sites, 492 gynecologic cancer patients were screened for seven open clinical trials during the study period. This included 170 (34.5 %) ovarian cancer patients, 156 (31.7 %) endometrial cancer patients, and 119 (24.2 %) cervical cancer patients. Over 40 % had advanced stage disease, and 10.6 % had recurrent disease. Only three patients were identified as having a relevant open trial; none ultimately enrolled due to not meeting trial eligibility criteria. An additional 2-52 patients were retrospectively found to have a relevant trial available despite not being identified as such within the electronic screening log system. Up to 14.4 % of patients had one or more missing minimum data elements that hindered full evaluation of clinical trial availability. Re-screening patients when new trials open may identify 12-15 additional patients per recurrent disease trial. Conclusions:An electronic screening log system can increase awareness of gynecologic oncology clinical trials at a NCI-designated cancer center's community partner sites. However, it is inadequate as a single intervention to increase clinical trial enrollment. Providing adequate support staff, documenting clinical factors consistently, re-screening patients at relevant intervals, and coordinating with central study personnel may increase its utility.